hum0335-v2Release info

Research on new diagnosis and clinical picture of lymphoproliferative diseases by combining genetic analysis and immunological traits

Aims

Diagnosis of lymphoproliferative diseases, except for typical cases, is often pathologically difficult, and diagnosis has long been based on chromosome analysis, immunological traits, and genetic abnormalities. Recent advances in the comprehensive analysis of genetic abnormalities and immunological studies have led to a number of reports of new abnormalities and features that can lead to diagnosis, but diagnosis in clinical practice has not kept pace with these changes. In this study, we compared the clinical picture, including prognosis, of the current pathological diagnosis with that of a new diagnosis based on comprehensive analysis of genetic mutations and immunological traits that have not yet been incorporated into conventional clinical practice.

Methods

[Target capture] We created primers covering the coding regions of ARID1A, NOTCH2, CXCR4, MYD88, PRDM1, CD274, PDCD1LG2, RAG2, KMT2D, MYBBP1A, TP53, and CD79B and performed targeted sequencing using the NextSeq 500 next-generation sequencer. After annotation based on GRCh37/hg19, mutations that met the following criteria were filtered out: Read Depth < 500, Alt Variant Freq < 5% (< 1% on MYD88 L265P), global frequency > 1% or East Asian pop frequency > 1% based on 1000 Genomes Project, synonymous mutations, inflame mutations, and missense mutations scored "tolerated" by SIFT or "benign" by PolyPhen.
[Whole exome sequencing] Library was made according to Agilent SureSelect Target Enrichment System protocol.

Participants/materials

[Target capture] DNAs extracted from specimens from 10 cases of Waldenström macroglobulinemia and 10 cases of non IgM-type lymphoplasmacytic lymphoma (LPL)
[Whole exome sequencing] DNAs extracted from bone marrow cells (after transformation) of one patient with T cell lymphoproliferative disease (probably diagnosis is a transformation case from T-LGL (Large Granular Lymphocytic Leukemia), though we don't have definitive diagnosis for both indolent disease and aggressive disease of transformation.

URL

N/A

Principal investigator

Akihiko Yokohama

Affiliation

Division of Blood Transfusion Service, Gunma University

No use of the controlled access data has been recorded.